The invention features graftable polymers including biologically active agents and the use of such polymers in the manufacture of shaped articles.
Polymeric materials have been widely used for manufacturing of medical devices such as artificial organs, implants, medical devices, vascular prostheses, blood pumps, artificial kidney, heart valves, pacemaker lead wire insulation, intra-aortic balloon, artificial hearts, dialyzers and plasma separators, among others. The polymer used within a medical device must be biocompatible (e.g., must not produce toxic, allergic, inflammatory reactions, or other adverse reactions). It is the physical, chemical and biological processes at the interface, between the biological system and the synthetic materials used, which defines the short- and long-term potential applications of a particular device. In general, the exact profile of biocompatibility and biodegradation, including chemical and physical/mechanical properties i.e., elasticity, stress, ductility, toughness, time dependent deformation, strength, fatigue, hardness, wear resistance, and transparency for a biomaterial are extremely variable.
The polymeric coating of a medical device may also serve as a repository for delivery of a biologically active agent. Where the active agent is a pharmaceutical drug, it is often desirable to release the drug from the medical device over an extended period of time. Most systems for kinetically controlled direct drug delivery employ a polymer. For example, the agent may be released as the polymer enzymatically degrades or disintegrates in the body or may diffuse out of the polymeric matrix at a controlled rate. A site-specific drug transfer system can produce a high concentration of agent at the treatment site, while minimizing the adverse effects associated with systemic administration.
In order to maintain the effectiveness of the polymeric coating, non-productive surface degradation or erosion should be minimized such that sufficient quantities of the drug-releasing polymer remain available for the required duration of pharmaceutical activity. One representative pathway of surface erosion is the flaking of the surface of a blended polymer. The use of excess amounts of a pharmaceutically active polymer is one means by which sufficient quantities of drug may be ensured. The administration of excess amount of drug and drug-containing polymer, however, may lead to the release of drug beyond an optimal time frame. Such outcomes may lead to undesirable side effects in patients. In the manufacture of shaped articles using blends of base polymers with polymers that include biologically active agents, reducing the proportion of the base polymer in order to accommodate increased amounts of pharmaceutically active polymers may adversely affect the mechanical properties of the shaped article. As a result, there is a need for pharmaceutically active polymers, polymer surfaces, shaped articles, and implantable medical devices with increased longevity that will maintain pharmaceutical efficacy for the desired time period as well as retain the desirable properties of the base polymer.